The research program is designed to further explore the adaptations that attend the loss of functional renal mass. Dogs with chronic renal insufficiency (CRI) provide a model for long term studies, not only for the investigation of metabolic perturbations but for exploring amplified biological oscillations after an acute challenge. Thereby, CRI exchances the opportunity for uncovering physiologic compensating and regulatory mechanisms. A systematic investigation of the degree and nature of potassium disposition by extra-renal tissues after an acute potassium load is proposed. Particular emphasis is placed on the contribution of the sympathetic nervous system (circulating and synaptic catecholamines, Alpha and Beta mediated effects). Other factors (glucagon, insulin, aldosterone) will be studied in-vivo. In-vitro studies are proposed as well. Integrity of the calcium-phosphorus-parathyroid hormone-vitamin D axis in CRI will be defined. 1) The sequential effects of variations in dietary calcium and phosphorus and their effects on bone and renal responses to exogenous PTH will be assessed and correlated with circulating levels of parathyroid hormone and vitamin D metabolites; 2) the photoproduction of vitamin D will be examined; 3) the biochemical nature of the final steps in the PTH response will be detailed in normal and remnant kidneys by identifying and characterizing protein kinases(s), phosphorprotein phosphatase(s) and phosphoprotein substrates that undergo phosphorylation/dephosphorylation in tubular brush border membranes.